Phase II year
2013
(last award dollars: 2014)
Phase II Amount
$3,620,218
The objective of this proposal is to complete engineering development and pre-clinical testing of a transapical miniaturized ventricular assist device (tMVAD) to treat patients with less advanced heart failure (HF). HF is increasing worldwide and represents a major burden in terms of health care resources and costs. Despite advances in medical care, prognosis with HF remains poor, especially in advanced stages. Currently, LVAD therapy, though increasing (4,000 cases/year), has not yet met the clinical demand (> 100,000 HF patients/yr). It requires a major operative intervention, arrested heart with cardiopulmonary bypass (CPB), and blood component exposure, which have been associated with significant adverse event rates and longer recovery periods. To overcome these limitations, HeartWare (Miami Lakes, FL) has developed a miniaturized transapical left ventricular assist device (tMVAD). Unlike other MCS devices currently in clinical trials, the tMVAD is significantly smaller in size and weight and only requires a single insertion through the apex of the left ventricle. The tMVAD is designed for intraventricular implantation with an outflow cannula that crosses the aortic valve. The device can be inserted via a minimally-invasive approach (subcostal incision or mini-thoracotomy) to access the LV apex, and eliminates the need for creation of the preperitoneal pocket, and anastomosis of the outflow graft. The tMVAD consists of a pedestal section that is attached to the epicardial surface near the left ventricular (LV) apex, a standpipe that carries the drive cables for the motor externally to the LV, a pump housing that contains the tMVAD core assembly and a vane diffuser, and a self-centering outflow cannula positioned across the aortic valve. The technological advantages and clinical benefits of the tMVAD include antegrade flow, beating heart surgery with no CPB, and ease of implant (and removal) that enables physicians to treat patients with less advanced HF, improve patient outcomes shorten recovery time, and lower hospital costs. In this phase II proposal, we will complete engineering development and pre-clinical testing of the tMVAD to support a FDA submission for phase one (n=10) and phase two (n=300) clinical trials. To achieve this objective, we will complete the engineering development and design freeze of the tMVAD in compliance with Good Manufacturing Practices (GMP) specifications for a human implant quality system; demonstrate efficacy and biocompatability of the tMVAD by completing Validation and Verification (V&V) testing (fatigue), anatomical fit and surgical procedure study (human cadaver, n=10), and in vivo acute (n=8) and chronic 90- day (n=8) studies in a bovine model; and demonstrate long-term safety and reliability of the tMVAD in normal (N, n=8) and chronic ischemic heart failure (IHF, n=8) animals in a 90-day Good Laboratory Practices (GLP) study. The GLP study design includes statistical comparison of normal and ischemic heart failure bovine model in control (no LVAD support) to test (tMVAD support) groups. The pre-clinical GLP, V&V, and GMP study data will be used to support an IDE application for a clinical trial in patients with advanced heart failure. Our long- term goal is to successfully translate the HeartWare tMVAD into clinical practice to treat earlier stage HF patients to achieve improved patient outcomes and restore their quality of life.
Public Health Relevance Statement: Public Health Relevance: HeartWare (Miami Lakes, FL) is developing a transapical miniaturized ventricular assist device (tMVAD) that can be implanted using a less invasive surgical procedure (subcostal or mini-thoracotomy) on a beating heart ('off pump') without cardiopulmonary bypass (CPB). The clinical benefits of the HeartWare tMVAD include the opportunity to treat patients with less advanced HF for bridge-to-transplant (BTT), destination therapy (DT), and/or bridge-to-recovery (BTR), which will shorten recovery time and lower hospital costs while improving patient outcomes and quality of life.
Project Terms: Acute; Adoption; Adverse event; Anastomosis - action; Anatomy; Animals; aortic valve; base; biomaterial compatibility; Biomedical Engineering; Blood; blood pump; Cadaver; Cannulas; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cardiovascular system; Caring; Cattle; China; Chronic; Clinical; Clinical Engineering; clinical practice; Clinical Trials; commercialization; Core Assembly; cost; cost effective; Data; design; Destinations; Development; Device Removal; Devices; Engineering; Equipment Malfunction; Excision; Fatigue; Fluoroscopy; follow-up; Freezing; functional outcomes; Goals; good laboratory practice; Government Agencies; Healthcare; Heart; Heart Arrest; Heart failure; Hemolysis; Hemorrhage; Hospital Costs; Housing; Human; Implant; implantation; improved; in vivo; India; innovation; Institutes; Intervention; Intraventricular; Left; Left ventricular structure; Marketing; Medical; meetings; Metric; miniaturize; minimally invasive; Modeling; Motor; Myocardial Ischemia; next generation; Operative Surgical Procedures; Outcome; outcome forecast; Patients; Phase; phase 1 study; Physicians; Positioning Attribute; pre-clinical; product development; public health relevance; Publishing; Pump; Quality of life; Recovery; research clinical testing; Research Design; Research Personnel; research study; Resources; Safety; sample fixation; Secure; Staging; success; Support Groups; Surface; Surgical incisions; System; Target Populations; Techniques; Testing; Thoracotomy; Thrombosis; Time; Titania; Titanium; Translating; Transplantation; Tube; Ventricular; ventricular assist device; verification and validation; Weight
